Treatment Of Gastrointestinal Cancer Research Articles

Vaccinia virus-mediated oncolytic immunotherapy: emerging strategies for gastrointestinal cancer treatment at dawn

Vaccinia virus-mediated oncolytic immunotherapy: emerging strategies for gastrointestinal cancer treatment at dawn

Enhanced Detection of Gastrointestinal Malignancies using Machine Learning-Optimized Liquid Biopsy: A Mini Review.

Gastrointestinal (GI) cancers represent some of the most common and lethal malignancies globally, underscoring the urgent need for improved diagnostic strategies. Traditional diagnostic methods, while effective to some degree, are often invasive and unsuit-able for regular screenings. This review article explores integrating machine learning (ML) with liquid biopsy techniques as a revolutionary approach to enhance the detection and monitoring of GI cancers. Liquid biopsies offer a non-invasive alternative for cancer detection through the analysis of circulating tumor DNA (ctDNA) and other biomarkers, which when combined with ML, can significantly improve diagnostic accuracy and patient outcomes. We conducted a comprehensive review of recent advancements in liquid biopsy and ML, focusing on their synergistic potential in the early detection of GI cancers. The review addresses the application of next-generation sequencing and digital droplet PCR in enhancing the sensitivity and specificity of liquid biopsies. Machine learning algorithms have demonstrated remarkable ability in navigating complex datasets and identifying diagnostically significant patterns in ctDNA and other circu-lating biomarkers. Innovations such as machine learning-enhanced "fragmentomics" and tomographic phase imaging flow cytometry illustrate significant strides in non-invasive cancer diagnostics, offering enhanced detection capabilities with high accuracy. The integration of ML in liquid biopsy represents a transformative step in the early detection and personalized treatment of GI cancers. Future research should focus on overcoming current limitations, such as the heterogeneity of tumor-derived genetic materials and the standardization of liquid biopsy protocols, to fully realize the potential of this technol-ogy in clinical settings.

Assessment of microbiome signature for predicting prognosis of gastrointestinal cancers

The gut microbiome has emerged as a crucial factor in the prognosis and progression of gastrointestinal cancers, though its mechanisms remain largely unknown. This review aims to provide a comprehensive summary of the current research on the use of gut microbiome signatures as prognostic biomarkers in gastrointestinal cancers. We present an overview of emerging studies that explore microbial signatures as biomarkers for different gastrointestinal cancers, and explore the potential benefits and limitations of using these signatures as prognostic tools. Finally, we discuss how these microbial signatures can be harnessed to improve the detection, prevention, and treatment of gastrointestinal cancers.

Pigment Epithelial-Derived Factor in Pancreatic and Liver Cancers-From Inflammation to Cancer.

Gastrointestinal (GI) cancers are among the leading causes of mortality worldwide. Despite the emergence of new possibilities that offer hope regarding the successful treatment of these cancers, they still represent a significant global health burden. These cancers can arise from various cell types within the gastrointestinal tract and may exhibit different characteristics, behaviors, and treatment approaches. Both the prognosis and the outcomes of GI treatment remain problematic because these tumors are primarily diagnosed in advanced clinical stages. Current biomarkers exhibit limited sensitivity and specificity. Therefore, when developing strategies for the diagnosis and treatment of GI cancers, it is of fundamental importance to discover new biomarkers capable of addressing the challenges of early-stage diagnosis and the presence of lymph node metastases. Pigment epithelial-derived factor (PEDF) has garnered interest due to its inhibitory effects on the migration and proliferation of cancer cells. This protein has been suggested to be involved in various inflammation-related diseases, including cancer, through various mechanisms. It was also observed that reducing the level of PEDF is sufficient to trigger an inflammatory response. This suggests that PEDF is an endogenous anti-inflammatory factor. Overall, PEDF is a versatile protein with diverse biological functions that span across different tissues and organ systems. Its multifaceted activities make it an intriguing target for therapeutic interventions in various diseases, including cancer, neurodegeneration, and metabolic disorders. This review, for the first time, summarizes the role of PEDF in the pathogenesis of selected GI cancers and its potential utility in early diagnosis, prognosis, and therapeutic strategies for this malignancy.

Validating a simplified financial toxicity screening tool for patients with cancer.

318 Background: Medical-related financial hardship (called financial toxicity) can negatively impact patient clinical outcomes and overall well-being. Routine financial toxicity screening is recommended to facilitate referrals to resources for patients experiencing, or at risk for, financial toxicity. The validated Comprehensive Score for Financial Toxicity (COST) tool is widely used in research to measure financial toxicity; however, its 11-question length and lack of standardized screening threshold make it challenging to implement in clinical practice. This analysis sought to develop and validate an abbreviated version of the tool, suitable for routine screening in clinical practice. Methods: The full COST was administered as part of clinical care from June 2022-August 2023. Patients receiving treatment for breast, gynecologic, thoracic, or gastrointestinal cancer at an urban comprehensive cancer center were queried via patient portal or in clinic. Using 38,330 observations, we calculated the correlation of abbreviated tools of varying length with the full COST score (0-44, lower scores=higher FT). We then used a validation dataset of 19,196 observations to assess the positive and negative predictive values (PPV, NPV) of an abbreviated tool against the full COST score, when compared to thresholds for risk previously used in the literature (score ≤15, ≤20). Results: Including two questions (Q3: “I worry about the financial problems I will have in the future as a result of my illness or treatment”; Q6: “I am satisfied with my current financial situation”) yielded r=0.922 correlation with the full COST. For this 2-item tool, PPV ranged from 74-91%, and NPV ranged from 91-98% when compared to the full COST tool. Table 1 shows the PPV and NPV of varying score thresholds for the abbreviated COST against full scores ≤15 and ≤20. Conclusions: Using a large and clinically diverse sample of patients with cancer,we demonstrate the predictive value of an abbreviated COST tool and show its approximate accuracy when compared to the full tool. Simplified, clinically integratedscreening for financial hardship can efficiently ensure appropriate intervention for patients experiencing medical-related financial hardship and can also be a first step toward mitigating hardship among those at risk for developing it. Predictive value of 2-item COST vs. full COST score in the validation set. Full COST score ≤ 15 Yes No 2-question, COST score ≤ 1 Yes 2337 (14%) 253 (1.5%) PPV = 90% No 822 (4.8%) 13844 (80%) 1-NPV = 5.6% Full COST score ≤ 15 Yes No 2-question, COST score ≤ 2 Yes 2924 (17%) 1045 (6.1%) PPV = 74% No 235 (1.4%) 13052 (76%) 1-NPV = 1.8% Full COST score ≤ 20 Yes No 2-question, COST score ≤ 2 Yes 3626 (21%) 343 (2.0%) PPV = 91% No 1199 (6.9%) 12088 (70%) 1-NPV = 9.0% Full COST score ≤ 20 Yes No 2-question, COST score ≤ 3 Yes 4359 (25%) 1272 (7.4%) PPV = 77% No 466 (2.7%) 11159 (65%) 1-NPV = 4.0%

Barriers to serious illness conversations in patients with advanced cancer: A mixed methods study.

228 Background: Serious illness conversations (SICs) are discussions between oncology clinicians and patients with cancer about illness understanding and care preferences. SICs are associated with less intensive and more goal-concordant care near the end of life, but many patients die without an SIC. Methods: PATH-SIC is an ongoing, single-center randomized trial (NCT05629065) that enrolls adults without a documented SIC starting a treatment for breast, gastrointestinal, genitourinary, gynecologic, or lung cancers with an expected prognosis of less than one year. The trial examines the effects of clinician- and patient-nudges on SIC documentation within 60 days of patient’s randomization to one of four arms (no nudge, clinician nudge, patient nudge, or both). This embedded mixed methods study recruited patients who still did not have an SIC 60 days from randomization, their caregivers (if present at time of consent) and oncologists. Interviews explored patients’ and caregivers’ 1) experiences with SICs, 2) perceptions about why SICs may not occur, and 3) suggestions to empower others to initiate SICs. Participating oncologists were surveyed by email. We used qualitative content analysis and descriptive statistics to identify themes. Results: The study included 44 participants: 19 patients, 10 caregivers and 15 oncologists. Patients had a median age of 63 years, were 63% female and 58% White and 68% had gastrointestinal cancers. Though no patient had a documented SIC, patients and their oncologists often disagreed about whether an undocumented SIC had occurred previously (Table). Patients’ and caregivers’ reported barriers to SICs included patient factors (lack of readiness, desire to maintain hope, focus on the present), clinician factors (perceived discomfort with prognostic disclosure and SICs), and prognostic uncertainty (current disease control, unpredictable prognosis). Patients’ and caregivers’ reported facilitators to SICs included patient- (self-advocacy, SIC readiness), clinician- (comfortable rapport), disease- (progression, worsening symptoms), and family-related facilitators (advocates for the patient to engage in SICs). To increase SICs, patients and caregivers reported greater acceptance of interventions involving a personal touch (e.g. phone call) over automated processes. Oncologist survey responses were brief. They reported SICs were most frequently triggered by disease progression or treatment intolerance, and recommended longer appointment times and written materials to facilitate SIC. Conclusions: Patient, caregiver and oncologist feedback on barriers and facilitators to SICs provided useful insights to improve interventions to encourage SICs. Patient/oncologist dyad (n=16) concordance of prior SICs. # of dyads Agreed SIC occurred 7 Agreed SIC did not occur 2 Only oncologist reported SIC 6 Only patient reported SIC 1 Total patient/oncologist dyads 16

Design and Modelling of Continuum Robot for Endoscopic Submucosal Dissection Surgery With Lifting Force Estimation.

Endoscopic submucosal dissection (ESD) is an effective treatment for early-stage gastrointestinal cancers. However, traditional surgical instruments lack accuracy and force-sensing. A new type of continuum robot for ESD is designed. An accurate static model of the proposed continuum robot is established, considering cases where the robot bends into C-shapes and S-shapes. A force estimation method based on an accurate static model is proposed. Then, the accuracy of the static model and force estimation is verified through experiments. Finally, an ex-organ experiment is carried out. The average position error of the proposed static model is 0.72mm, accounting for 2.57% of the total robot length. The average error of force estimation is 19.53mN. By gripping and cutting ex-porcine gastric mucosa, the robot's functionality is validated. This paper contributes to precise control and safe interaction of continuum robots.

Temperature-sensitive injectable chitosan-based hydrogel for endoscopic submucosal dissection

Endoscopic submucosal dissection (ESD) is an effective treatment for polyps and early gastrointestinal cancers, but requires a high level of operator skill. Injecting submucosal materials (SIM) helps create a fluid cushion between the mucosal and muscular layers, making the procedure easier and reducing associated risks. However, SIMs commonly used in current clinical practice tend to spread quickly and fail to provide long-lasting submucosal fluid cushions (SFC). Thus, there is a critical need for a material that is easy to inject while also maintaining a durable barrier. We prepared succinylated hydroxybutyl chitosan (HBC-SA) by adding succinic anhydride (SA) to hydroxybutyl chitosan (HBC). The hydrogel had excellent temperature-sensitive properties and was able to be injected via an endoscopic injection needle even after gel formation. In vitro and in vivo studies showed that it has satisfactory biocompatibility. Functional experiments showed that the submucosal lifting properties of this hydrogel were significantly better than that of normal saline (NS) and sodium hyaluronate (SH), two commonly used clinical materials. In addition, the hydrogel possessed excellent hemostatic properties. Based on these results, HBC-SA is a promising candidate for submucosal injection during ESD.

Evaluation of chemotherapy toxicities in patients receiving treatment for gastrointestinal cancers and therapeutic monitoring of 5-fluorouracil as a clinical support tool.

5-Fluorouracil (5-FU) is essential in treating gastrointestinal cancers, but some patients show severe toxicity. The toxicity is exposure-related, which is linked to the enzyme dihydropyrimidine dehydrogenase (DPD) decoded by the DPYD gene. This study aimed to evaluate the possible toxicity related to 5-FU plasma levels, DPYD genotyping, and DPD phenotyping. Forty-seven gastrointestinal cancer patients receiving 5-FU were included in this study. 5-FU plasma levels and DPD phenotyping were analyzed by UPLC-MS/MS. DPYD genotyping was also assessed. The Common Terminology Criteria for Adverse Events (CTCAE) was used to classify the toxicity. For hematological toxicity, 27.65% showed neutropenia, 78.72% anemia, and 29.78% thrombocytopenia. The area under the curve (AUC) of 5-FU calculated from the plasma was evaluated for three treatment cycles, and we observed that at the initial cycle, 48.93% were underexposed and 10.63% were overexposed, with a total of 59.56% of patients outside the therapeutic range. In the DPYD genotyping, 97.87% of patients had a wild-type genotype, and 2.12% had c.1236G>A mutation (E412E, rs56038477). A total of 82.97% of patients showed a phenotype compatible with normal DPD activity. These findings suggest that the evaluation of DPYD genotyping and DPD phenotyping in the Brazilian population still requires further study. Moreover, the analysis of the plasma AUC of 5-FU could contribute to clinical routine, being a very useful tool, especially for identifying patients outside the therapeutic range and thus guiding more individualized doses, or even in the intervention of possible toxicities related to overexposure.

Changes in Skeletal Muscle Mass in the First 3 Months Following Gastrointestinal Cancer Surgery: A Prospective Study.

Surgical resection is the primary treatment for gastrointestinal (GI) cancers, but postoperative skeletal muscle loss (SML) is common and linked to poor prognosis. This study aims to identify patterns of muscle change, examine its association with quality of life (QoL), and explore predictors of SML in the first 3 months. A prospective cohort study was conducted on patients newly diagnosed with GI cancer and undergoing surgery in China between September 2021 and May 2022. Skeletal muscle mass (SMM) and QoL were assessed at admission, 7 days, 1 month, and 3 months post-surgery. Demographic, clinical data, and biomarkers were collected. Missing data were imputed using multiple imputation. Data were analyzed using growth mixture modelling, bivariate analyses, and logistic regression. A total of 483 patients completed baseline assessment. Of the 242 patients with complete muscle assessments, 92% experienced SML. Three distinct patterns of muscle change were identified: 57% had normal preoperative SMM with mild postoperative SML, 16% had low preoperative SMM with moderate SML, and 27% had normal preoperative mass but severe postoperative SML. Moderate/severe SML was associated with more postoperative complications, poorer health, and higher symptom burden. Independent predictors included advanced age, preoperative sarcopenia, advanced cancer stage, and low prognostic nutrition index (PNI ≤ 45). The results did not change when using imputed values. Although SML is prevalent, patterns of muscle change are heterogeneous among patients. Advanced age, preoperative sarcopenia, advanced cancer stage, and cancer-related inflammation are predictors for moderate/severe SML, highlighting the need for early detection and management.

Particle therapy in gastrointestinal cancer-a narrative review.

Radiation therapy is one of the main pillars in the treatment of gastrointestinal (GI) cancers, especially esophageal and anorectal malignancies. The worldwide standard of care is yet an irradiation with photons. Though not commonly used, charged particles offer some physical advantages with a highly conformal dose distribution, which allows an even better sparing of organs at risk. In addition to dosimetric advantages, heavy-ion beams like carbon ions may offer an additional set of biological advantages. Because particle therapy is not standard of care, data are scarce-especially concerning the use in GI malignancies. The aim of this review is to provide a compact overview of the currently available literature. PubMed and Web of Science databases were searched for publications on particle radiotherapy in GI cancer (e.g., proton therapy in esophageal cancer, carbon ion radiotherapy in pancreatic cancer). Here we present a review of the current data on particle therapy with regard to esophageal, pancreatic, hepatic and anorectal malignancies. Data on particle therapy in GI cancer are scarce. Nevertheless, the current literature shows some promising results. Further clinical evidence, especially randomized trials, is crucial to augment the role of particle radiotherapy in GI cancer.

Association of pre-existing cardiovascular disease with administration of fluoropyrimidine chemotherapy in patients with gastrointestinal malignancies

ObjectiveFluoropyrimidine chemotherapy is a first-line treatment for many gastrointestinal (GI) cancers, however, cardiotoxicity concerns may limit administration in patients with pre-existing cardiovascular disease (CVD). This study investigated the association of...

Incorporating Tumor Genomic Profiling and Circulating Tumor Cell-derived Organoids into Clinical Practice for Gastrointestinal Cancers.

Precision medicine aims to revolutionize healthcare by tailoring treatment regimens. This study aimed to integrate comprehensive tumor genomic profiling (CTGP) by targeted-gene panel sequencing and drug screening by circulating tumor cell-derived organoids (CTOs) into clinical practice for the treatment of gastrointestinal (GI) cancers. Nine patients with various GI cancers underwent CTGP and CTO drug sensitivity testing. CTGP results guided targeted therapy and immunotherapy, while CTO drug sensitivity predicted response to chemotherapy and targeted agents. The drug recommendations from two platforms were correlated with the treatment response to the suggested medications retrospectively. Five patients received therapies aligned with CTGP, including HER2-targeted treatment, immunotherapy, and BRAF/MEK dual inhibition, showing positive responses. CTO drug sensitivity predicted progression under regorafenib (low potential benefit) and good response to chemotherapy with high potential benefit. The combination of CTGP and CTO drug sensitivity may exhibit significant correlation with clinical outcomes during treatment with candidate drugs, demonstrating a sensitivity of 79% and an accuracy of 75%. This encompasses various treatment modalities, such as chemotherapy, targeted therapy, and immunotherapy. The present investigation elucidated the integration of CTGP and CTO drug sensitivity screening into clinical practice in a complementary manner, showcasing a significant correlation between treatment response and testing outcomes. Additional prospective evaluation of these two testing modalities in a large cohort is warranted to confirm whether the inclusion of CTO drug sensitivity screening confers enhanced survival benefits compared to utilizing CTGP alone.

Immune checkpoint inhibitors and radiotherapy in gastrointestinal cancer treatment

Background. In recent decades, immunotherapy has become a topical area of research in the complex treatment of oncological diseases. A significant achievement in the immunotherapy of oncological diseases was the discovery of immune checkpoint proteins, which are effective inhibitors of the immune response. Immune checkpoint inhibitors (ICIs) have been approved for the treatment of certain gastrointestinal malignancies. However, the clinical efficacy of ICIs monotherapy remains low. To improve the outcome of treatment, numerous studies are conducted in which immunotherapy is combined with other standard methods of anticancer treatment. Radiation therapy (RT) may enhance the antitumor immune response when combined with ICIs and is worth considering when combined with immunotherapy. The effectiveness of the combined strategy is actively being investigated in clinical trials. Purpose – to highlight the latest achievements in the field of combined use of immunotherapy with ICIs and RT in malignant neoplasms of the gastrointestinal tract. Materials and methods. Data searches for the review were conducted using PubMed, Scopus, Google Scholar, and ClinicalTrials.gov databases. The data of works published in 2013-2023 were analyzed and systematized. Results and discussion. The rationality of the combination of RT and immunotherapy was substantiated. The results of the combined use of neoadjuvant chemoradiotherapy (CRT) and immunotherapy with ICIs in patients with resectable esophageal cancer and combined treatment in patients with advanced disease are analyzed. The clinical results of the use of ICIs in combination with RT or CRT in patients with gastric cancer and the combination of ICIs and RT in patients with hepatocellular carcinoma are presented. The clinical effects of adding ICIs to neoadjuvant RT or CRT in patients with locally advanced and borderline resectable pancreatic cancer and the results of trials of a combined strategy in patients with advanced disease are characterized. The clinical efficacy of the combined approach in locally advanced rectal cancer, which is a routine area of RT application, and in metastatic disease is reviewed. The results of small studies of combined treatment involving patients with metastatic colorectal cancer are presented. Conclusions. Over the past decade, research in the field of immunotherapy for gastrointestinal tumors has increased significantly. Based on the synergistic effects of radiation therapy and immune checkpoint inhibitors, the combination of these therapeutic approaches is increasingly being tested in gastrointestinal cancer to improve treatment outcomes. Published studies have shown encouraging results with satisfactory toxicity. However, most clinical trials are retrospective, non-comparative phase I/II trials and are limited to a small number of patients. The results of these studies can serve as a basis for conducting multicenter prospective studies with large sample sizes to confirm the effectiveness of combined therapy.

A phase 1 study of biweekly nab-paclitaxel/oxaliplatin/S-1/LV for advanced upper gastrointestinal cancers: TCOG T1216 study.

Oxaliplatin- and fluoropyrimidine-based triplet regimens have demonstrated feasibility and efficacy in the treatment of upper gastrointestinal (UGI) cancers. Herein, we evaluate the feasibility and preliminary efficacy of biweekly nab-paclitaxel plus oxaliplatin and S-1/leucovorin (SOLAR) in chemonaïve UGI cancers. A 3 + 3 phase 1 study was conducted to determine the maximal tolerated dose (MTD) of oxaliplatin in SOLAR (nab-paclitaxel [150 mg/m2 in D1], oxaliplatin [60, 75, or 85 mg/m2 in D1], and oral S-1/leucovorin [35 mg/m2 and 30 mg bid from D1 to D7]). The secondary endpoints were overall response rate (ORR), progression-free survival (PFS), overall survival (OS), and safety. Thirteen and 6 accruals were in the dose-escalation and MTD expansion cohorts, respectively. One of 6 patients at level III experienced dose-limiting toxicity (grade 3 diarrhea), which revealed that the MTD of oxaliplatin was 85 mg/m2. After a mean of 15.9 cycles of treatment, the most common treatment-related grade 3/4 toxicities were neutropenia (57.9%) and diarrhea (21.1%). The ORR was 63.2%. The median PFS and OS were 12.5 and 24.7 months, respectively. The current study revealed the MTD of oxaliplatin and demonstrated the preliminary efficacy of SOLAR in UGI cancers, which deserves further investigation. NCT03162510.

The Effect of Artemisia sieberi (Dermeneh Dashti) Plant Extract on the Expression of Genes Involved in the Apoptosis Signaling Pathway in the HT_29 Cell Line

Background: Colorectal cancer (CRC) is one of the most common malignant tumors in humans. The influence of natural plant compounds is widely acknowledged today. Artemisia sieberi has anti-bacterial, anti-fungal, and anti-inflammatory properties. Objectives: The aim of the forthcoming study is to investigate the impact of Artemisia sieberi plant extract on the expression of key genes within the apoptosis signaling pathway of the HT-29 cell line. Methods: In this study, RNA extraction and cDNA synthesis were conducted subsequent to the culturing and treatment of HT-29 cancer cells with plains herb extract. A real-time PCR test utilizing specific primers for Bax and Bcl-2 was then performed using the Rotor-Gene Q machine. Additionally, an MTT assay was conducted to assess the toxicity of the Artemisia sieberi extract. Results: The test revealed that as the concentration of the studied extract increased, cell viability decreased in a dose-dependent manner. The calculated IC50 value for the plains herb extract was found to be 0.44 µg/mL. Furthermore, the levels of Bax and Bcl-2 genes in cells treated with the plains herb extract were determined to be 1.48 and 0.45, respectively, indicating an increase in the expression of these two genes. Conclusions: Given the low toxicity of the Artemisia sieberi extract observed in the MTT test and its potential to increase the expression of apoptosis-inducing genes in intestinal cells, it appears that Artemisia sieberi extract could be employed as a therapeutic supplement for the prevention and treatment of gastrointestinal cancers.

Patient Experiences of Specialty Palliative Care in the Perioperative Period for Cancer Surgery

ContextThough patients undergoing treatment for upper gastrointestinal (GI) cancers frequently experience a range of sequelae and disease recurrence, patients often do not receive specialty palliative care soon after diagnosis and it is unknown in what ways they may benefit. ObjectivesTo understand patient experiences of specialty palliative care in the perioperative period for patients seeking curative intent upper GI oncologic surgery. MethodsAs part of a randomized controlled trial, we conducted in-depth interviews between November 2019 and July 2021 with 23 patients in the intervention arm who were undergoing curative intent treatment for upper GI cancers and who were also followed by the specialty palliative care team. ResultsWe found five themes that characterized patient experiences and perceptions of specialty palliative care. Patients typically had limited prior awareness of palliative care (theme 1), but during the study, came to understand it as a “talking” intervention (theme 2). Patients whose concerns aligned with palliative care described it as being impactful on their care (theme 3). However, most patients expressed a focus on cure from their cancer and less perceived relevance for integration of palliative care (theme 4). Integrating specialist palliative care practitioners with surgical teams made it difficult for some patients to identify how palliative care practitioners differed from other members of their care team (theme 5). ConclusionWhile receipt of specialty palliative care in the perioperative period was generally perceived positively and patients appreciated palliative care visits, they did not describe many needs typically met by palliative care practitioners. Trial Registrationclinicaltrials.gov registration: NCT03611309.

YB-800, a monoclonal antibody targeting the human neuronal pentraxin receptor (NPTXR), as a potential candidate for the design of a first in class antibody drug conjugate (ADC) as novel therapeutic intervention in gastro-intestinal cancers.

e15022 Background: The human neuronal pentraxin receptor (NPTXR) gene encodes a type II transmembrane protein that functions as a trans-synaptic organizer and anchors neuronal pentraxin complexes to plasma membranes. Beside a subset of neuronal cells (Hippocampus and Cerebral Cortex), expression of NPTXR is not detected in all other tissues [ The Human Protein Atlas database]. In recent studies [Kanda et al. (2020) Mol. Cancer. doi: 10.1186/s12943-020-01251-0], transcriptome and bioinformatics analysis of gastric cancer (GC) tissues from patients with or without metastasis have revealed that NPTXR expression was associated with disease progression. NPTXR expression was also correlated negatively with survival in GC patients. It appears that NPTXR does not have a major physiological function; e.g., NPTXR−/− mice showed no abnormalities in reproduction, development, metabolism, or motor function. NPTXR is expressed in a number of GI cancers, i.e., gastric, esophageal, colorectal, pancreatic, bladder, liver, as well as breast and thyroid cancer. YB-800 is a fully humanized monoclonal antibody against NPTXR (identified by in silico analysis). Methods: The present studies were conducted to provide a rationale for the design of a YB-800-based antibody drug conjugate (ADC) for therapeutic intervention in oncology. Hence, YB-800 binding to and internalization in selected tumor cells, as well as immunohistochemistry (IHC) in tumor biopsies, were evaluated. Results: Taken together experimental data confirm that: (i) YB-800 binds to a new target (NPTXR) on selected tumor cells; confirmed by FACS analysis; (ii) IHC analysis in tumor samples demonstrates specific immunoreaction in bladder, gastric, prostate, hepatocellular carcinoma, colorectal cancer and cervical cancer, but not in adjacent healthy tissues; and (iii) once YB-800 binds to NPTXR, the conjugate is internalized in selected tumor cells in a time-dependent manner. Conclusions: In conclusion, YB-800 represents a first in class ADC candidate that could be used as novel treatment for gastro-intestinal cancers. Hence, as initial proof of concept, tesirine (DNA intercalating agent) and deruxtecan (topoisomerase I inhibitor) containing protease-sensitive linkers were coupled to YB-800 by stochastic maleimide conjugations to interchain cysteines. Initial results with YB-800-based ADCs will be discussed.

Emerging Technologies in Endoscopy for Gastrointestinal Neoplasms: A Comprehensive Overview.

Gastrointestinal neoplasms are a growing global health concern, requiring prompt identification and treatment. Endoscopic procedures have revolutionized the detection and treatment of gastrointestinal tumors by providing accurate, minimally invasive methods. Early-stage malignancies can be treated with endoscopic excision, leading to improved outcomes and increased survival rates. Precancerous lesions, like adenomatous polyps, can be prevented by removing them, reducing cancer occurrence and death rates. Advanced techniques like chromoendoscopy, narrow-band imaging, and confocal laser endomicroscopy improve the ability to see the mucosa surface and diagnose conditions. Artificial Intelligence (AI) applications in endoscopy can enhance diagnostic accuracy and predict histology outcomes. However, challenges remain in accurately defining lesions and ensuring precise diagnosis and treatment selection. Molecular imaging approaches and therapeutic modalities like photodynamic therapy and endoscopic ultrasonography-guided therapies hold potential but require further study and clinical confirmation. This study examines the future prospects and obstacles in endoscopic procedures for the timely identification and treatment of gastrointestinal cancers. The focus is on developing technology, limits, and prospective effects on clinical practice.

Implementing financial toxicity and health-related social risks screening and referral.

11006 Background: Financial toxicity (FT), or cancer-related economic hardship, is associated with delayed/skipped care, reduced quality of life, and worse mortality. Screening for FT and health-related social risks (HRSR) as part of assessment for social determinates of health is currently being integrated into clinical care, but there is limited research on outcomes after patients screen positive for FT or HRSR. Methods: We conducted FT and HRSR screening for patients receiving treatment for breast, gynecologic, gastrointestinal, or thoracic cancer at an urban comprehensive cancer center. Screening included the 11-item Comprehensive Score for Financial Toxicity (COST) tool (scored 0-44, lower scores = worse FT) and a HRSR checklist to identify food, housing, medicine, and transportation insecurity. A COST score ≤20 or any endorsed HRSR was considered a positive screen, and financial/assistance counseling referral was offered. Multivariable logistic regression assessed associations of accepting referral, after controlling for demographic and clinical characteristics. Data were collected 09/2022-08/2023. Results: 28,606 patients completed screening, of which 32% (n = 9106) screened positive. Median COST was 16.0. Identified HRSR were: 23% food, 25% housing, 21% medicine, and 24% transportation insecurity. Of positive screens, 51% (n = 4683) requested some form of financial counseling. Associations with accepted referral include: higher FT (β = 1.15, 95% CI: 1.13, 1.16), younger age (β = 1.01, 95% CI: 1.008, 1.02), more essential needs (β = 1.19, 95% CI: 1.13, 1.25), non-White race/ethnicity (β = 1.70, 95% CI: 1.49, 1.93), and stage 3 (β = 1.29, 95% CI: 1.08, 1.53) or stage 4 (β = 1.26, 95% CI: 1.07, 1.49) diagnoses (vs. stage 0/1). Needs of patients who requested counseling included concerns relating to out-of-pocket expenses (68%), non-medical expenses (39%), health insurance coverage (23%), and paying for prescription medication (18%; not mutually exclusive). Of financial counseling sessions with available dispositions (n = 2336/4683, 50%), outcomes (not mutually exclusive) included general counseling (29%), referral to specific assistance programs (e.g., copay assistance, reduced cost care program; 15%), and insurance navigation (15%). One-third of patients requesting counseling did not respond to contact attempts; 21% reported no longer being interested in counseling upon contact. Conclusions: Screening for FT and HRSR was feasible, and one-third of patients were identified as at risk for FT or having an unmet essential need. Patients known to have worse FT outcomes (those with later-stage disease, younger age, higher FT, minoritized groups) were more likely to accept financial counseling; however, only one-half of those at risk accepted help. Future work will focus on improving workflows to ensure assistance meets patient needs, including addressing patient stigma around requesting help.